Wednesday, December 20, 2006

Well just got an email from Chris Surridge of PLoS One saying their Beta Site is open to the public. I am excited by this new journal and system and plan to submit many of our papers there. People should check it out for themselves and hopefully give comments to them to make the system better. Some detail from the email is given below.

The first paper there that struck my eye is a paper on polyploidy in halophilic Archaea. This paper, by Sebastian Breuert, Thorsten Allers, Gabi Spohn, and Jörg Soppa suggests that polyploidy is more common in archaea than was previously appreciated.

----------------------------The email says:

Before your first visit, I want to let you know about the inherent challenges of this project and the philosophy that compels PLoS to confront them.

We want to speed up scientific progress and believe that scientific debate is as important as the investigation itself. PLoS ONE is a forum where research can be both shared and commented upon - we are launching it as a beta website so that the whole scientific community can help us develop the features.

What makes the site beta? Not the content, which features peer-reviewed research from hundreds of authors across a diverse range of scientific disciplines. It's the additional tools and functionality surrounding these papers that will be continually refined and developed in response to user feedback.

It is this union of continually evolving user tools provided by the Topaz publishing platform and extensive content that will make PLoS ONE a success.

....

The first beta release of PLoS ONE features tools that allow users to annotate articles and participate in discussion threads. Our goal is to spark lively discussion online and we'd like to invite you to participate. Future updates will include user ratings for both papers and the comments made about them, personalized content alerts and much more.

We will be watching with interest to see how our new platform and software responds to high volumes of traffic and encourage you to give your feedback on your first experience via the site itself.

Tuesday, December 19, 2006

Here is an Open Access must read. Bill Hooker blogs about pushing the Open Access envelope in the area of Open Data. That is, making sure the raw data from a scientific study is available. Although there are many efforts for this, he discussed something I have never really considered which is trying to make sure the journals do not somehow obtain rights to the raw data (e.g., by having it placed onto their site as Supplemental Information).

He has a suggested protocol for adding an addendum to the typical copyright agreement one might make with a journal, which is, in my mind, a great first step.

This site is a collection of audio and video of lectures that were for the "Microbes, Minerals, and the Environment" symposium. The collection includes talks by David Stahl, Derek Lovely, Anna Louise Reysenbach, Faroq Azam, Jonathan Zehr, and Paul Falkowski, all relating to microbes in the enviornonment. I have not watched all of them but the ones I have seen are quite good.

Well, the good news keeps pouring in for science education and the teaching of evolution. The Cobb County School Board, which had tried to insert religious points of view into the teaching of evolution, have backed down. They had placed stickers on biology textbooks that read

This textbook contains material on evolution. Evolution is a theory, not a fact, regarding the origin of living things. This material should be approached with an open mind, studied carefully and critically considered

Yet, of course they did not label any other area of science in this way. AP reports that

It is nice to see that they have had a change of heart, or at least have realized that they would lose this fight. Either way, science and education win this round. Unfortunately, the proponents of Intelligent Design, will try again and again. And they should be fought every step of the way to keep them from attacking the teaching of evolution in science classes.

All these recent stories on the Neanderthal sequencing projects reminded me of a short story I wrote while in graduate school. I wrote this story for a class taught by Carl Djerassi, a professor at Stanford and an author of a variety of what he calls "Science in Fiction" novels. In these, he writes about the workings of science and thus the name of the genre.

For this class all the students were supposed to write short stories that were then shared among the students and with Djerassi and each week we would read and discuss two of the stories. The stories written by the other students were great overall - moving and interesting and fun to read and discuss. The class digressed at the end due to Djerassi's desire for the group to write a fiction "Renga." Renga is a form of poetry where one person writes a line and then another writes the next line and together a group is supposed to come up with a poem of interest.

So we wrote a story - with each student in the class writing a paragraph and then sending it on to the next author. In the end, the story was, in my opinion, much worse than all the individual's stories. But amazingly, Djerassi convinced Nature to publish the story and thus I am a co-author on what was the first (and probably last) short story published in Nature. The worst part of it was - Nature made us reduce the lenght of the story to fit some page restrictions. That would be fine I guess if we knew this in advance. But in the end, what this did was cause us to edit the story and remove any hints of the "Renga" nature of the story. I was embarassed by the story and wanted to use a pen name so people would not know it was me. I chose Joan Eisen but for some very particular reasons I had to change my author line back to Jonathan (long story).

OK -back to the main point. I wrote a story that is about sequencing Neanderthal DNA. And though I am not sure any more what I think of the story ... here it is.

David Cohn was unaware that, while he was camping in Death Valley, every five minutes his computer would contact U. C. Berkeley's mainframe system and download any email messages David had received since the last check. David did not find out that he had left his email program open until, fumbling for his keys outside his office, he heard his computer play two randomly selected segments of Mozart's clarinet concerto, announcing that two new messages had just arrived. David had been gone for three weeks and had come in early in the morning so he could check his email in peace before other people would arrive and start asking about his trip or reading his email over his shoulder.

Symposium ThemeMicroscopic organisms-including viruses, bacteria, archaea, and single-celled eukaryotic organisms-comprise the vast majority of life on the planet, yet startling little is known about their true diversity and the multitudinous roles that they play in the ecosphere. The knowledge that we do have tends to come from either those organisms that can be cultured in the laboratory (estimated to be <1% of all species) or those that make us or other organisms that are important to us sick. The revolution of using DNA sequences to discover and describe microbial diversity has drastically altered our view of the microbial world and its players, however. Less than two decades ago, using ribosomal RNA gene sequences, Carl Woese and colleagues proposed an entirely new classification of life, that of three domains of organisms-Bacteria, Archaea, and Eukarya-in opposition to the traditional five-kingdom schema. Now, new biochemical processes, including new forms of photosynthesis and even electricity-generating bacteria are being discovered as culture-independent and broader explorations into new habitats are performed. Yet, at the same time that we begin to uncover new hidden potential benefits of microorganisms, the news is also replete with stories of so-called emergent diseases that threaten humans as well as other organisms on the planet.

This symposium will bring together a diverse group of microbiologists and conservation biologists to explore this intersection of two fields that, until now, has not been considered in depth. We hope to address the broad questions of: How much microbial diversity is there on the planet? How does this diversity affect other organisms, both positively and negatively? How should conservation practices take microbial life into account?

Audience: This symposium will bring together scientists from the traditionally disparate fields of microbiology and conservation, including biogeochemists, marine microbiologists, disease ecologists, and microbial systematists. as well as conservation practitioners, wildlife managers, policy makers, educators, students, and interested members of the general public.

SPECIAL STUDENT PRICING WILL BE OFFERED!

CALL FOR POSTERS: The symposium will include a poster session. Details for content guidelines and abstract-submission requirements are available at http://cbc.amnh.org/symposia/microbes/.

TO RECEIVE SYMPOSIUM UPDATES AS THEY BECOME AVAILABLE, email biodiversity@amnh.org.

Thursday, December 14, 2006

There can be no greater nightmare for a medical worker than to be accused of harming their patients. Even worse, if the allegations are untrue. Yet this is exactly what has happened to six health workers who have been sentenced to death for spreading HIV among Libyan children. Today we publish urgently an essay from Council on Foreign Relations Senior Fellow and Pulitzer Prize winning author Laurie Garrett, that warns of the terrible dangers not just to these workers but to health workers worldwide, and their patients in the poorest parts of the world if the executions go ahead. The essay is part of an increasing chorus of condemnation in scientific journals including Science and Nature . AAAS has a website which gives information on how anyone can add their voice to this campaign.

Sunday, December 10, 2006

I am starting a new series here ---- finding and writing about classic papers in Evolution and Genetics and Molecular Biology that are available for free in Pubmed Central. And though plenty of classic papers are not avilable, a good collection of them are.

My first selection is Luria and Delbrück's paper from 1943 on the origin of mutations. This papers is near and dear to my heart in many ways and I still remember looking it up for the first time when I was an undergraduate. I was taking a class from Jennifer Doudna on the origin of life, and we had to write a paper as part of the class. In the class we had discussed a new paper by John Cairns and colleagues that revisitid the origin of mutations question. Cairns et al. result suggested to them at least that bacteria could pick and choose the mutations they needed for increased fitness in a particular situation (suggestive of so-called Lamarckian evolution to them). I was fascinated by this work (so much so, that it became the topic of my grad. school application essays and the topic of my first two years of PhD research in Phil Hanawalt's Lab). So I chose to write a paper on the origin of mutations.

Obviously, to write such a paper I had to go to Luria and Delbrück's work since they were the first to experimentally test the question of how much mutations pre-existed selection and how much they arose after selection. I stillremember sifting through the old journals in the library at Harvard to find this and turning the pages in teh dust covered volume to read it.

Luria and Delbrück chose as their experimental system resistance to bacteriaphage and their model organism, Escherichia coli. In their paper first the describe the theoretical underpinning of their wor. In their theory they come up with a way to do an experiment to test whether mutations pre-exist selection or arise in response to it - something now generally known as a fluctuation test. Basically the idea is simple. Take a particular form of the bacteria. Innoculate multiple test tubes with a small amount and let each test tube grow up to a dense culture. Then expose bacteria from each tube to the selective pressure. If the mutations pre-exist selection then there should be big differences between the replicate test tubes in the number of mutants since in some the mutation would arise early in the growth of the culture and in some they would arise late (this is known as a jackpot distribution). If the mutations arise after selection then each tube should have somewhat similar numbers (with some variation around a mean).

And when they did the experiments the results followed very closely the jackpot model. They stated:

We consider the above results as proof that in our case the resistance to virus is due to a heritable change of the bacterial cell which occurs independently of the action of the virus. It remains to be seen whether or not this is the general rule. There is reason to suspect that the mechanism is more complex in cases where the resistant culture develops only several days after lysis of the sensitive bacteria.

And thus they showed that mutations unequivocally pre-exist selection. Now, it turns out that their experiment had a flaw - since they were using a lethal selection (phage) the system did not really allow for a long period of time for the mutations after selection to arise (when your dead it is hard to generate mutations). The Cairns experiment (and Ryan's before him) showed that some unusual results occurred if you used a non lethal selection. So one cannot really use Luria and Delbrück's experiment to disprove the possibility that mutations arise after selection. Nevertheless, their proof that mutations can exist before selection was a fundamental discovery. And their methods were used throughout bacterial genetics for years (to this day in fact). For more detail see Access Excellence page about Luria and Delbruck.

This is such a fundmentally important paper, and it is great that this paper is available, free to all, in Pubmed Central. See below:

I took my daughter to Petco the other day again. We treat it as a zoo/aquarium which works perrty well. They have lots of fish, birds, mice, and other animals and she loves it. I know, it probably does not treat the animals exceptionally well, and I do not buy animals from there. But my daughter loves fish and this is a great way for her to see some without going too far.

If you are into cycling in any way, you should check out the route for Stage 2 of the Amgen Tour of California. The race, which will likely feature a collection of some of the top pro cyclists in the world, is coming through Davis on February 20, 2007. And they even give Davis a little plug:

Continuing east past Lake Berryessa, the peloton will head through Davis, recently named the best cycling town in the U.S. by Bicycle Magazine.

It should be a good day for the town, although I hope it is not raining too heavily. I am not sure what the plans are for closing roads and/or for town activities on that day, so if anyone out there knows anything please let me know.

From the map it looks like they will take Russell through town and then sneak on up to Covell to Road 102 and then on towards Woodland. It also looks like there will be a bonus sprint in town.

Friday, December 08, 2006

The New York Times ran an obituary today for Esther Lederberg, who passed away on November 11. Dr. Lederberg was one of the giants of microbiology and her research was the precursor for multiple Nobel Prizes and laid the groundwork for much of the molecular biology revolution. Among her many amazing pieces of work:

The isolation of lambda phage, a virus that infects the bacterium E. coli. This virus has been used as a model system for studying the molecular basis of life.

She and her husband invented replica plating, a method that revolutionized bacterial genetics.

Amazingly to me, and thanks to Pubmed Central and the American Society of Microbiology, her replica plating paper is available for free online here.

All microbiologists out there should read this paper and should say thanks for the work of a true giant in the field.

Here is another somewhat hidden gem in Davis. We have a 22 month old daughter. She gets rapidly bored with new toys. My wife discovered a great way around this. Every few weeks she goes to the Davis Resource LIbrary and Toy Closet provide by the city Child Care Services. For a $10 annual fee, you can check out up to five toys and five videos/books at a time. Although sometimes it is hard to take the toys back if our daughter becomes particularly fond of them, she always ends up enkoying the trips to select new toys. From their web site:

The Toy and Resource Library is located at 600 A Street, in Davis. Library hours are Monday through Friday from 8:00 a.m. to 4:30 p.m.

So if you have kids who get a little bored with their toys and you do not want to keep buying new ones, check out the library. Most of the toys are in great shape and the books there have also been popular in our house.

Thursday, December 07, 2006

OK. I know I am not supposed to do this. But hey, are there really any rules for blogs?

I got my first major local press story since moving to Davis yesterday. The Sacramento News and Review ran a cover story on the U. C. Davis Genome Center, featuring me, Katie Pollard, and the director of the center Richard Michelmore. I of course do not recall saying any of the things that I am quoted saying but I certainly recall saying things close to what was quoted so in this case the reporter (Ralph Brave) seems to have done a fair job. I guess I would quibble a tiny bit with my portrayal in terms of the discussion of synthetic biology (I believe it is a powerful tool but that the practitioners downplay the risks).

The best part of the story - they featured my work on the glassy winged sharpshooter symbionts that we published in PLoS Biology earlier this year. That is (hopefully) good for me since the sharpshooter is a big deal out here in N. California since it is a vector for Pierce's Disease in grapes. Plus, they were able to use a figure from my paper since of course, the paper in fully Open Access. So my work gets some extra exposure that might have been more difficult for the paper to pull off if it was published in a non Open Access journal. In essence, Open Access publishing is the gift that keeps on giving. As long as I keep getting credit for it, it is great for me that people do not have to get permission or pay a fee to use figures from my papers.

Wednesday, December 06, 2006

Scientists from NASA have reported what appears evidence that not has Mars has water in the past, but that it has flowed on the Martian surface in the last seven years. When comparing photographs of the same site in 1999 and 2005 taken by the orbiting Mars Global Surveyor, the scientists found

appearance of a lightly-shaded patch that has all the hallmarks of being caused by water bubbling up from under the Martian surface and running down the 30 degree slope

While there may be other explanations, the pictures are stunning. If this is water, I think we have to start to come to grips with the high probability that life will be found on Mars. In other words, not only might life have existed there in the past, but I think it is reasonably likely that there is life there now. Now before you get all hoity toity on me - I am not talking about little green men here. But possibly little green microbes. Or little pale microbes that use chemical energy to fix carbon and grow. Such microbes are of course all over earth, in the deep sea, in hot springs, in tidal flats, in animal guts. The real questions (again, if this is really water) the become:

could life have evolved separately on Mars?

could microbial life from Earth have seeded Mars?

I think the answers to both questions, though unclear, could potentially be yes. For question 1, if we look at the origin of life on Earth, most studies now suggest it happened over a relatively short time scale (a few hundred million years) and possibly much faster. It may in fact have been somewhat inevitable - as long as the conditions for chemical evolution were present in the Early earth. This chemical evolution could have then set up the possibility for life to have evolved. Though the exact steps are unclear for the origin of life on Earth, it is not far fetched to imagine that they could have occured on Mars as well.

As for question 2 - I think life easily could have been transported between the two planets. All you really need is for a meteorite or comet collision with Earth to blast some moderately sized pieces of material off of Earth into space. Microbes in such material could have survived for some period of time on such pieces in space (remember, many microbes do not need oxygen, and can survive incredibyl harsh conditions on Earth). Imagine if a big piece of Earth was knocked off the planet - microbes in the center of such a piece would be protected from some of the radiation and other stresses of space. And you just need one of these pieces to end up on Mars for the cross-seeding event to occur. Of sure, there are a series of assumptions here and a multiplication of low probability events. But we can make up for low probability by multiplying by 3.5 or so billion years - the amount of time that life has existed on Earth.

So this raises one final issue for me. The person with the greatest job title in the world - John Rummel, better get moving. He is the "Planetary Protection Officer" for NASA - charged with protecting other planets from Earth and Earth from other planets. One of his main jobs is to think about how to make sure the Martian missions do not bring microbes with them to Mars so that if microbes are found there we can assume they are from Mars not earth. Unfortunately in my google searches about this it seems Dr. Rummel has been promoted within NASA and I cannot figure out who took over his old job. Does that alas mean we are temporarily without a planetary protection officer? I hope not.

Whether it turns out life exists or existed on Mars or not, the finding of apparently flowing water on the surface is wildly exciting and proof to me that Mars missions are critical to our understanding of the world around us.

Friday, December 01, 2006

There is a potentially controversial and very interesting article in the journal PLoS Pathogens on Flu Evolution. The study was led by Edward Holmes at Penn State, and co-authored by many researchers including colleagues of mine at my former institution TIGR. They performed a detailed evolutionary analysis of the cmplete genomes of 413 influenza A viruses of the H3N2 type (the H#N# system refers to the subtypes of Hemaglutanin and Neuraminidase genes).

The virus genomes were sequenced at TIGR using a high throughput flu viral genome sequencing protocol originally developed at described by Elodie Ghedin and colleagues here and here. The viruses they selected were from across New York State as part of a surveillance program.

Using a variety of evolutionary analyses including phylogenetic reconstructions and examination of substitution patterns, they come to a surprising conclusion - that

stochastic processes are more important in influenza virus evolution than previously thought, generating substantial genetic diversity in the short term

This may seem somewhat uninteresting to many out there but if true it is critically important in fighting flu and in understanding viral pathogen evolution. Right now there are substantial efforts to try and predict what future dominant flu strains will look like. These predictions tend to rely on assumptions that positive selection of viruses is critical in generating and maintaining diversity. If stochastic processes are as important as Holmes et al conclude, it would mean that more intensive monitoring of flu is needed in almost real time (since predicting random events tends to be, well, very hard).

I confess I have not tried to evaluate whether or not I think their conclusions are correct, but on first glance they seem sound. This just goes to show that general genomic surveys that try to be relatively unbiased in their sampling can reveal substantial novel patterns not seen before in highly target genome sequencing projects.